AMPK Promotes Xenophagy through Priming of Autophagic Kinases upon Detection of Bacterial Outer Membrane Vesicles.
Cell Rep
; 26(8): 2150-2165.e5, 2019 02 19.
Article
em En
| MEDLINE
| ID: mdl-30784596
ABSTRACT
The autophagy pathway is an essential facet of the innate immune response, capable of rapidly targeting intracellular bacteria. However, the initial signaling regulating autophagy induction in response to pathogens remains largely unclear. Here, we report that AMPK, an upstream activator of the autophagy pathway, is stimulated upon detection of pathogenic bacteria, before bacterial invasion. Bacterial recognition occurs through the detection of outer membrane vesicles. We found that AMPK signaling relieves mTORC1-mediated repression of the autophagy pathway in response to infection, positioning the cell for a rapid induction of autophagy. Moreover, activation of AMPK and inhibition of mTORC1 in response to bacteria is not accompanied by an induction of bulk autophagy. However, AMPK signaling is required for the selective targeting of bacteria-containing vesicles by the autophagy pathway through the activation of pro-autophagic kinase complexes. These results demonstrate a key role for AMPK signaling in coordinating the rapid autophagic response to bacteria.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Classe III de Fosfatidilinositol 3-Quinases
/
Proteína Homóloga à Proteína-1 Relacionada à Autofagia
/
Membrana Externa Bacteriana
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Macroautofagia
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá